Ferguson Elaine A, Lugelo Ahmed, Czupryna Anna, Anderson Danni, Lankester Felix, Sikana Lwitiko, Dushoff Jonathan, Hampson Katie
Boyd Orr Centre for Population and Ecosystem Health, School of Biodiversity, One Health & Veterinary Medicine, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.
Environmental Health and Ecological Sciences Department, Ifakara Health Institute, Ifakara, Tanzania.
bioRxiv. 2025 Jan 16:2024.10.03.616420. doi: 10.1101/2024.10.03.616420.
Vaccination programs are the mainstay of control for many infectious diseases. Heterogeneous coverage is hypothesised to reduce vaccination programme effectiveness, but this impact has not been quantified in real systems. We address this gap using fine-scale data from two decades of rabies contact tracing and dog vaccination campaigns in Serengeti district, Tanzania. We also aimed to identify drivers of continued circulation of rabies in the district despite annual vaccination campaigns. Using generalised linear mixed models, we find that current focal (village-level) dog rabies incidence decreases with increasing recent focal vaccination coverage. However, current focal incidence depends most on recent incidence, both focally and in the wider district, consistent with high population connectivity. Removing the masking effects of prior non-focal incidence shows that, for the same average prior non-focal (wider-district) vaccination coverage, increased heterogeneity in coverage among the non-focal villages leads to increased focal incidence. These effects led to outbreaks following years when vaccination campaigns missed many villages, whereas when heterogeneity in coverage was reduced, incidence declined to low levels (<0.4 cases/1,000 dogs annually and no human deaths) and short vaccination lapses thereafter did not lead to resurgence. Through transmission-tree reconstruction, we inferred frequent incursions into the district each year (mean of 7). Inferred incursions substantially increased as a percentage of all cases in recent years, reaching 50% in 2022, suggesting regional connectivity is driving residual transmission. Overall, we empirically demonstrate how population connectivity and spatial heterogeneity in vaccination can impact disease outcomes, highlighting the importance of fine-scale monitoring in managing vaccination programs.
疫苗接种计划是控制许多传染病的主要手段。据推测，接种覆盖率的不均一性会降低疫苗接种计划的效果，但这种影响在实际系统中尚未得到量化。我们利用来自坦桑尼亚塞伦盖蒂区二十年狂犬病接触者追踪和犬类疫苗接种活动的精细数据来填补这一空白。我们还旨在确定尽管每年都开展疫苗接种活动，但该地区狂犬病仍持续传播的驱动因素。通过广义线性混合模型，我们发现当前重点区域（村级）犬类狂犬病发病率随着近期重点区域疫苗接种覆盖率的提高而降低。然而，当前重点区域的发病率在很大程度上取决于近期重点区域和更广泛区域的发病率，这与高人口连通性相一致。消除先前非重点区域发病率的掩盖效应表明，在相同的平均先前非重点区域（更广泛区域）疫苗接种覆盖率下，非重点村庄之间接种覆盖率的异质性增加会导致重点区域发病率上升。这些影响导致在疫苗接种活动遗漏许多村庄的年份之后出现疫情暴发，而当接种覆盖率的异质性降低时，发病率降至低水平（每年<0.4例/1000只犬，且无人类死亡），此后短暂的疫苗接种间隔并未导致疫情复发。通过传播树重建，我们推断每年有频繁的狂犬病传入该地区（平均7次）。近年来，推断出的传入病例占所有病例的百分比大幅增加，在2022年达到50%，这表明区域连通性正在推动残留传播。总体而言，我们通过实证证明了人口连通性和疫苗接种的空间异质性如何影响疾病结果，突出了精细监测在管理疫苗接种计划中的重要性。
